Effect of intravenous immunoglobulin therapy in recurrent implantation failure: A Systematic review and meta-analysis

IVIg is a pooled donor immunoglobulin preparation, used for auto-immune and inflammatory diseases. In assisted reproduction it receives considerable scepticism. Clinical data is expanding, but individual studies may be perceived as weak, meaning an updated appraisal of evidence in implantation failure is needed.

To assess the efficacy of IVIg in Recurrent Implantation Failure (RIF) following assisted reproductive technology.

Systematic review and meta-analysis of randomized controlled trials and observational studies comparing IVIg therapy against placebo in a defined RIF population.

A comprehensive literature search, identifying studies involving RIF following ART, using pre-conception IVIg. Primary outcomes were clinical pregnancy (CPR), live birth (LBR), implantation (IR), and miscarriage rates (MR). The selection process yielded twelve studies, including 1023 cases and 2276 controls.

A significant increase in CPR (OR=5.14, 95 % CI: 2.33-11.30, p<0.001) and LBR (OR=4.60, 95 % CI:2.44-8.68, p<0.001) is demonstrated in IVIG-treated patients, with an improvement in IR (OR=2.35, 95 % CI: 1.04-5.29, p=0.039) and reduction in MR (OR=0.60, 95 % CI: 0.37-0.97, p=0.036). Substantial heterogeneity was identified across studies, which was addressed through subgroup analyses, assessing if the variability in may be attributed to study-specific factors.

IVIg may enhance implantation, clinical pregnancy, and live birth rates in RIF patients, underscoring benefit for specific populations. Positive immunological risk factors may predict potential candidates, but it could also be of use in unexplained RIF with high-grade embryos. These findings highlight the importance of personalized therapeutic strategies to improve ART outcomes for complex cases.